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Principal Investigator: Anna Bukiya
Organization: UNIVERSITY OF SOUTH FLORIDA
Fiscal Year: 2024
Award: $435,815
Funding agency: National Institute on Alcohol Abuse and Alcoholism
In the United States, fetal alcohol spectrum disorders (FASD) represent the leading preventable cause of birth
defects and neurodevelopmental delay with life-long implications. FASD affects an estimated 40,000 infants in
the US each year, with 2-5% of younger school-age children having FASD. Currently, prediction of FASD
during pregnancy is not available, and there are no readily available cures against FASD. It is widely believed
that early detection of FASD and its subsequent intervention strategies are critical to allow earliest and most
effective therapeutic interventions. While fetal alcohol exposure targets multiple organs and systems, the brain
constitutes the most severely affected organ, exhibiting both structural and functional abnormalities. As
neuronal development critically depends on the oxygen delivery, nutritional supply and waste removal by
cerebral circulation, recent studies have been paying increasing attention to the fetal cerebral circulation as a
critical target of maternal alcohol consumption. However, the timing and mechanisms that govern fetal
cerebrovascular response to alcohol remain elusive. One of the major obstacles that preclude rapid
advancement of the studies on fetal cerebral circulation is lack of high-resolution imaging technique that would
be suitable for imaging of small lab animal species. Current proposal is put forth by the collaborating teams of
bioengineers and cerebrovascular physiologists with the overall goal of delivering a high-speed 3D
photoacoustic tomography (PAT) that will allow non-invasive, simultaneous visualization of all the embryos in a
mouse utero and track their development into adulthood longitudinally to study the association between alcohol
exposure-induced changes in fetal hemodynamics and cerebrovascular outcome after birth. Another obstacle
to developing effective treatments to alleviate symptoms and develop preventive measures against FASD is a
relatively limited knowledge on relevant targets for alcohol, including targets within fetal cerebral arteries. In
this regard, current proposal will focus on cerebral artery mitochondria. Critical role of mitochondria in
regulating cerebral artery function is well documented, and there is no doubt that mitochondrial is one of the
major sensors for alcohol as shown in liver and neurons. In our recent pioneered work we documented
persistent up-regulation of fetal cerebral artery proteome in response to alcohol exposure during mid-
pregnancy. However, systematic studies on cerebral artery mitochondria alterations in response to prenatal
alcohol exposure remain to be performed and the role of alcohol targeting of fetal cerebral artery mitochondria
remains to be established. To overcome these obstacles in the field, we propose to complete three related
Aims: (1) We will optimize a high-speed PAT system for 3D high-resolution brain imaging of rodents; (2) We
will develop advanced software for improved PAT 3D image reconstruction and analysis; (3) We will trace
cerebrovascular morphological and functional changes following fetal alcohol exposure into adulthood, with the
focus on fetal cerebral vessel density, artery diameter and mitochondrial function.
Terms: <0-11 years old><21+ years old><3-D><3-D Images><3-D image><3-D visualization><3-Dimensional><3-dimensional visualization><3D><3D image><3D images><3D visualization><Abscission><Adult><Adult Human><Affect><Alcohol Chemical Class><Alcohols><Animals><Arteries><Assay><Attention><Autopsy><Bioassay><Bioenergetics><Biological Assay><Biomedical Engineering><Birth><Birth Defects><Blood flow><Brain><Brain Hypoxia-Ischemia><Brain Nervous System><Brain Vascular><Brain hemorrhage><Brain imaging><Cell Body><Cells><Cerebrovascular Circulation><Cerebrovascular system><Cerebrum><Characteristics><Child><Child Youth><Children (0-21)><Collaborations><Computer software><Congenital Abnormality><Congenital Anatomical Abnormality><Congenital Defects><Congenital Deformity><Congenital Malformation><Development><Developmental Delay><Developmental Delay Disorders><Diameter><Dysfunction><Early Diagnosis><Embryo><Embryonic><Encephalon><Excision><Exhibits><Extirpation><FASD><Fetal Alcohol Exposure><Fetal Alcohol Spectrum Disorder><Fetal ETOH Exposure><Fetal Ethanol Exposure><Fetus><Functional disorder><Genus Hippocampus><Gestation><Goals><History><Human><Image><Image Analyses><Image Analysis><Imaging Procedures><Imaging Technics><Imaging Techniques><In Utero Alcohol Exposure><In Utero ETOH Exposure><In Utero Ethanol Exposure><Infant><Intervention><Intervention Strategies><Knowledge><Liver><Metabolic><Mice><Mice Mammals><Mitochondria><Modern Man><Morphology><Murine><Mus><Nerve Cells><Nerve Unit><Neural Cell><Neurocyte><Neurons><Nutritional><O element><O2 element><Organ><Outcome><Oxygen><Oxygen Consumption><Parturition><Pharmacology><Physiopathology><Pregnancy><Prenatal Alcohol Exposure><Prenatal ETOH Exposure><Prenatal Ethanol Exposure><Preventative measure><Preventive measure><Proteome><Recording of previous events><Removal><Reporting><Research><Resolution><Rodent><Rodentia><Rodents Mammals><Role><School-Age Population><Seahorse><Software><Specific Child Development Disorders><Speed><Surgical Removal><System><T-state hemoglobin><Technology><Testing><Therapeutic Intervention><Three-Dimensional Image><Uncertainty><United States><Up-Regulation><Upregulation><Visualization><Work><adulthood><alcohol exposed><alcohol exposure><alcohol response><alcohol-exposed pregnancy><alleviate symptom><ameliorating symptom><bio-engineered><bio-engineers><bioengineering><biological engineering><bleeding in brain><blood flow in brain><blood vessels in the brain><brain blood circulation><brain blood flow><brain blood vessels><brain vascularization><brain vasculature><brain visualization><cerebral><cerebral artery><cerebral blood flow><cerebral blood vessel><cerebral circulation><cerebral vascular><cerebral vascularization><cerebral vasculature><cerebro-vascular><cerebrocirculation><cerebrovascular><cerebrovascular blood flow><cerebrovascular vessels><cerebrovasculature><de-oxyhemoglobin><decrease symptom><density><deoxyhemoglobin><developmental><doubt><early detection><effective therapy><effective treatment><ethanol exposed><ethanol exposure><ethanol response><exposed to alcohol><exposed to alcohol prenatally><exposed to ethanol><exposure to alcohol><exposure to ethanol><extracellular><fetal><fewer symptoms><fluorescence imaging><fluorescent imaging><gestation ETOH exposure><gestation alcohol exposure><gestation ethanol exposure><gestational ethanol exposure><hemodynamics><hemorrhagic stroke><hepatic body system><hepatic organ system><high resolution imaging><histories><hypoxia/ischemia><image construction><image evaluation><image generation><image interpretation><image reconstruction><imaging><imaging approach><imaging based approach><improved><in vivo monitoring><intervention therapy><interventional strategy><kids><maternal alcohol consumption><maternal alcohol drinking><maternal alcohol ingestion><maternal alcohol use><maternal ethanol use><metabolic rate><mitochondrial><necropsy><neuron development><neuronal><neuronal development><new drug target><new druggable target><new pharmacotherapy target><new therapeutic target><new therapy target><novel><novel drug target><novel druggable target><novel pharmacotherapy target><novel therapeutic target><novel therapy target><nutritious><optoacoustic imaging><optoacoustic tomography><pathophysiology><photoacoustic imaging><photoacoustic tomography><postmortem><pregnancy ETOH exposure><pregnancy alcohol exposure><pregnancy ethanol exposure><prenatally alcohol exposed><prenatally exposed to alcohol><reduce symptoms><relieves symptoms><resection><resolutions><response><response to alcohol><response to ethanol><school age><sensor><social role><symptom alleviation><symptom reduction><symptom relief><therapeutically effective><three dimensional><three-dimensional visualization><tool><wasting><youngster>